Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP)

Lindborg, Carter M.; Brennan, Tracy A.; Wang, Haitao; Kaplan, Frederick S.; Pignolo, Robert J.

doi:10.1016/j.bone.2017.09.016

Cited by 9 publications

(7 citation statements)

References 31 publications

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“…Clinical symptoms of a flare-up such as pain, swelling, erythema and warmth are non-specific, and it is not possible to predict whether the acute phase will end up with HO or will resolve ( 66 ). A multitude of inflammatory, chondrogenic and osteogenic bone markers have been investigated, and although some were markedly elevated in patients with FOP, none have shown an association with disease activity or been able to predict HO formation adequately ( 69 – 71 ).…”

Section: Determination Of Disease Activity In Fopmentioning

confidence: 99%

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

et al. 2021

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Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics.

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Section: Determination Of Disease Activity In Fopmentioning

confidence: 99%

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

et al. 2021

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“…Localized or systemic myopathy, chronic inflammation, atrophy, HO, prolonged immobilization or combination of factors could modulate the bioelectric properties of muscle tissue. An opportunity for further research may entail evaluation of EIM with other objective and more established methods such as imaging ( 18 F-NaF PET/CT, CT, X-Ray, and MRI) or quantification of circulating markers 18 , 33 – 35 .…”

Section: Discussionmentioning

confidence: 99%

Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography

Farid

Golden

Robicheau

et al. 2022

Sci Rep

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Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder involving skeletal dysplasia and heterotopic ossification (HO) of muscle and connective tissue. We aimed to define a novel biomarker in FOP that enables reliable assessment of musculoskeletal tissue integrity. Considering logistical difficulties that FOP patients often face, our goal was to identify an at-home biomarker technique. Electrical impedance myography (EIM) is a non-invasive, portable method that can inform on muscle health. 15 FOP patients (age 10–52) and 13 healthy controls were assessed. Using EIM, multiple muscle groups were characterized per participant in a 45-min period. The Cumulative Analogue Joint Involvement Scale (CAJIS) was implemented to determine mobility burden severity. We additionally evaluated physical activity levels via a Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaire. Relative to controls, FOP patients demonstrated significantly lower regional and whole-body phase values at 50 kHz and 100 kHz, indicating more diseased muscle tissue. Lower whole-body phase and reactance values, and higher resistance values, were associated with greater FOP burden (CAJIS score range: 4–30) and lower physical activity levels at 50 kHz and 100 kHz. This study points to the potential utility of EIM as a clinical biomarker tool capable of characterizing muscle integrity in FOP.

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“…Impaired osteochondrogenesis in FOP results not only in extraskeletal bone formation, but also in growth plate dysplasia, early osteoarthritis, and joint deformation [ 56 ]. The flare-ups in FOP are accompanied by an elevation of serum cartilage-derived retinoic acid-sensitive protein (CD-RAP), which is a biomarker of chondrogenesis [ 57 ]. Opposing to FOP [ 58 ] POH ossifications are formed by an intramembranous process in which mesenchymal cells differentiate directly into osteoblasts and form ossification centers [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

et al. 2022

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Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired) background, that is, it could be caused by musculoskeletal trauma, such as burns, fractures, joint arthroplasty (traumatic HO), or cerebral or spinal insult (neurogenetic HO). HO formation is caused by the differentiation of stem or progenitor cells induced by local or systemic imbalances. The main factors described so far in HO induction are TGFβ1, BMPs, activin A, oncostatin M, substance P, neurotrophin-3, and WNT. In addition, dysregulation of noncoding RNAs, such as microRNA or long noncoding RNA, homeostasis may play an important role in the development of HO. For example, decreased expression of miRNA-630, which is responsible for the endothelial–mesenchymal transition, was observed in HO patients. The reduced level of miRNA-421 in patients with humeral fracture was shown to be associated with overexpression of BMP2 and a higher rate of HO occurrence. Down-regulation of miRNA-203 increased the expression of runt-related transcription factor 2 (RUNX2), a crucial regulator of osteoblast differentiation. Thus, understanding the various functions of noncoding RNAs can reveal potential targets for the prevention or treatment of HO.

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Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP)

Abstract: These data support the further exploration of CD-RAP as a stage-specific biomarker of HEO in FOP.

Cited by 9 publications

References 31 publications

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

Fibrodysplasia Ossificans Progressiva: What Have We Achieved and Where Are We Now? Follow-up to the 2015 Lorentz Workshop

Diminished muscle integrity in patients with fibrodysplasia ossificans progressiva assessed with at-home electrical impedance myography

The role of miRNA and lncRNA in heterotopic ossification pathogenesis

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